Dataset Information

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

ABSTRACT: The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.

SUBMITTER: Fox ER

PROVIDER: S-EPMC3090190 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

Fox Ervin R ER Young J Hunter JH Li Yali Y Dreisbach Albert W AW Keating Brendan J BJ Musani Solomon K SK Liu Kiang K Morrison Alanna C AC Ganesh Santhi S Kutlar Abdullah A Ramachandran Vasan S VS Polak Josef F JF Fabsitz Richard R RR Dries Daniel L DL Farlow Deborah N DN Redline Susan S Adeyemo Adebowale A Hirschorn Joel N JN Sun Yan V YV Wyatt Sharon B SB Penman Alan D AD Palmas Walter W Rotter Jerome I JI Townsend Raymond R RR Doumatey Ayo P AP Tayo Bamidele O BO Mosley Thomas H TH Lyon Helen N HN Kang Sun J SJ Rotimi Charles N CN Cooper Richard S RS Franceschini Nora N Curb J David JD Martin Lisa W LW Eaton Charles B CB Kardia Sharon L R SL Taylor Herman A HA Caulfield Mark J MJ Ehret Georg B GB Johnson Toby T Chakravarti Aravinda A Zhu Xiaofeng X Levy Daniel D

Human molecular genetics 20110304 11

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure ...[more]

PMID: 21378095

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Project description:BACKGROUND:Using data from 4 community-based cohorts of African Americans, we tested the association between genome-wide markers (single-nucleotide polymorphisms) and cardiac phenotypes in the Candidate-gene Association Resource study. METHODS AND RESULTS:Among 6765 African Americans, we related age, sex, height, and weight-adjusted residuals for 9 cardiac phenotypes (assessed by echocardiogram or magnetic resonance imaging) to 2.5 million single-nucleotide polymorphisms genotyped using Genome-wide Affymetrix Human SNP Array 6.0 (Affy6.0) and the remainder imputed. Within the cohort, genome-wide association analysis was conducted, followed by meta-analysis across cohorts using inverse variance weights (genome-wide significance threshold=4.0?×10(-7)). Supplementary pathway analysis was performed. We attempted replication in 3 smaller cohorts of African ancestry and tested lookups in 1 consortium of European ancestry (EchoGEN). Across the 9 phenotypes, variants in 4 genetic loci reached genome-wide significance: rs4552931 in UBE2V2 (P=1.43×10(-7)) for left ventricular mass, rs7213314 in WIPI1 (P=1.68×10(-7)) for left ventricular internal diastolic diameter, rs1571099 in PPAPDC1A (P=2.57×10(-8)) for interventricular septal wall thickness, and rs9530176 in KLF5 (P=4.02×10(-7)) for ejection fraction. Associated variants were enriched in 3 signaling pathways involved in cardiac remodeling. None of the 4 loci replicated in cohorts of African ancestry was confirmed in lookups in EchoGEN. CONCLUSIONS:In the largest genome-wide association study of cardiac structure and function to date in African Americans, we identified 4 genetic loci related to left ventricular mass, interventricular septal wall thickness, left ventricular internal diastolic diameter, and ejection fraction, which reached genome-wide significance. Replication results suggest that these loci may be unique to individuals of African ancestry. Additional large-scale studies are warranted for these complex phenotypes.

Project description:ImportanceExtremely low diastolic blood pressure has been reported to be associated with increased adverse cardiovascular events (ie, the diastolic J-shape phenomenon); however, current US guidelines recommend an intensive blood pressure target of less than 130/80 mm Hg without mentioning the lower limits of diastolic blood pressure.ObjectivesTo evaluate whether there is a diastolic J-shape phenomenon for patients with an treated systolic blood pressure of less than 130 mm Hg and to explore the safe and optimal diastolic blood pressure ranges for this patient population.Design, setting, and participantsThis cohort study analyzed outcome data of patients at high cardiovascular risk who were randomized to intensive or standard blood pressure control and achieved treated systolic blood pressure of less than 130 mm Hg in the Systolic Blood Pressure Intervention Trial (SPRINT) and Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD-BP) trial. Data were collected from October 2010 to August 2015 (SPRINT) and from September 1999 to June 2009 (ACCORD-BP). Data were analyzed from January to May 2020.ExposureTreated diastolic blood pressure, divided in intervals of less than 60, 60 to less than 70, 70 to less than 80, and 80 mm Hg and greater.Main outcomes and measuresThe primary outcome was a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. A composite cardiovascular outcome, including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, was among the key secondary outcomes.ResultsA total of 7515 patients (mean [SD] age, 65.6 [8.7] years; 4553 [60.6%] men) were included in this analysis. The nominally lowest risk was observed at a diastolic blood pressure between 70 and 80 mm Hg for the primary outcome, the composite cardiovascular outcome, nonfatal myocardial infarction, and cardiovascular death. A mean diastolic blood pressure of less than 60 mm Hg was associated with significantly increased risk of the primary outcome (hazard ratio [HR], 1.46; 95% CI, 1.13-1.90; P = .004), the composite cardiovascular outcome (HR, 1.74; 95% CI, 1.26-2.41; P = .001), nonfatal myocardial infarction (HR, 1.73; 95% CI, 1.15-2.59; P = .008), and nonfatal stroke (HR, 2.67; 95% CI, 1.26-5.63; P = .01).Conclusions and relevanceThis cohort study found that lowering diastolic blood pressure to less than 60 mm Hg was associated with increased risk of cardiovascular events in patients with high cardiovascular risk and an treated systolic blood pressure less than 130 mm Hg. The finding that a diastolic blood pressure value between 70 and 80 mm Hg was an optimum target for this patient population merits further study.

Dataset Information

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

Publications

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

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